A glucagon analogue decreases body weight in mice via signalling in the liver
Abstract Glucagon receptor agonists show promise as components of next generation metabolic syndrome pharmacotherapies. However, the biology of glucagon action is complex, controversial, and likely context dependent. As such, a better understanding of chronic glucagon receptor (GCGR) agonism is esse...
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Nature Portfolio
2021
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oai:doaj.org-article:8c5c2844790d4fd68305731ce059ecb12021-11-21T12:18:37ZA glucagon analogue decreases body weight in mice via signalling in the liver10.1038/s41598-021-01912-02045-2322https://doaj.org/article/8c5c2844790d4fd68305731ce059ecb12021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01912-0https://doaj.org/toc/2045-2322Abstract Glucagon receptor agonists show promise as components of next generation metabolic syndrome pharmacotherapies. However, the biology of glucagon action is complex, controversial, and likely context dependent. As such, a better understanding of chronic glucagon receptor (GCGR) agonism is essential to identify and mitigate potential clinical side-effects. Herein we present a novel, long-acting glucagon analogue (GCG104) with high receptor-specificity and potent in vivo action. It has allowed us to make two important observations about the biology of sustained GCGR agonism. First, it causes weight loss in mice by direct receptor signalling at the level of the liver. Second, subtle changes in GCG104-sensitivity, possibly due to interindividual variation, may be sufficient to alter its effects on metabolic parameters. Together, these findings confirm the liver as a principal target for glucagon-mediated weight loss and provide new insights into the biology of glucagon analogues.Charlotte E. HindsBryn M. OwenDavid C. D. HopePhilip PickfordBen JonesTricia M. TanJames S. MinnionStephen R. BloomNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-7 (2021) |
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DOAJ |
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EN |
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Medicine R Science Q |
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Medicine R Science Q Charlotte E. Hinds Bryn M. Owen David C. D. Hope Philip Pickford Ben Jones Tricia M. Tan James S. Minnion Stephen R. Bloom A glucagon analogue decreases body weight in mice via signalling in the liver |
| description |
Abstract Glucagon receptor agonists show promise as components of next generation metabolic syndrome pharmacotherapies. However, the biology of glucagon action is complex, controversial, and likely context dependent. As such, a better understanding of chronic glucagon receptor (GCGR) agonism is essential to identify and mitigate potential clinical side-effects. Herein we present a novel, long-acting glucagon analogue (GCG104) with high receptor-specificity and potent in vivo action. It has allowed us to make two important observations about the biology of sustained GCGR agonism. First, it causes weight loss in mice by direct receptor signalling at the level of the liver. Second, subtle changes in GCG104-sensitivity, possibly due to interindividual variation, may be sufficient to alter its effects on metabolic parameters. Together, these findings confirm the liver as a principal target for glucagon-mediated weight loss and provide new insights into the biology of glucagon analogues. |
| format |
article |
| author |
Charlotte E. Hinds Bryn M. Owen David C. D. Hope Philip Pickford Ben Jones Tricia M. Tan James S. Minnion Stephen R. Bloom |
| author_facet |
Charlotte E. Hinds Bryn M. Owen David C. D. Hope Philip Pickford Ben Jones Tricia M. Tan James S. Minnion Stephen R. Bloom |
| author_sort |
Charlotte E. Hinds |
| title |
A glucagon analogue decreases body weight in mice via signalling in the liver |
| title_short |
A glucagon analogue decreases body weight in mice via signalling in the liver |
| title_full |
A glucagon analogue decreases body weight in mice via signalling in the liver |
| title_fullStr |
A glucagon analogue decreases body weight in mice via signalling in the liver |
| title_full_unstemmed |
A glucagon analogue decreases body weight in mice via signalling in the liver |
| title_sort |
glucagon analogue decreases body weight in mice via signalling in the liver |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/8c5c2844790d4fd68305731ce059ecb1 |
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